Insecticidal N-substituted sulfoximines

ABSTRACT

N-Substituted sulfoximines are effective at controlling insects.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. non-provisional applicationSer. No. 11/101,924 filed on 8 Apr. 2005, which claims priority fromU.S. provisional application 60/560,628 filed on 8 Apr. 2004. Thedisclosures of application Ser. Nos. 11/101,924 and 60/560,628 arehereby incorporated, in their entirety, by reference.

BACKGROUND OF THE INVENTION

The present invention concerns novel N-substituted sulfoximines andtheir use in controlling insects, particularly aphids. This inventionalso includes new synthetic procedures for preparing the compounds,pesticide compositions containing the compounds, and methods ofcontrolling insects using the compounds.

There is an acute need for new insecticides. Insects are developingresistance to the insecticides in current use. At least 400 species ofarthropods are resistant to one or more insecticides. The development ofresistance to some of the older insecticides, such as DDT, thecarbamates, and the organophosphates, is well known. But resistance haseven developed to some of the newer pyrethroid insecticides. Therefore aneed exists for new insecticides, and particularly for compounds thathave new or atypical modes of action.

SUMMARY OF THE INVENTION

This invention concerns compounds useful for the control of insects,especially useful for the control of aphids and other sucking insects.More specifically, the invention concerns compounds of the formula (I)

wherein

X represents NO₂, CN or COOR⁴;

L represents a single bond or R¹, S and L taken together represent a 5-or 6-membered ring;

R¹ represents methyl or ethyl;

R² and R³ independently represent hydrogen, methyl, ethyl, fluoro,chloro or bromo;

n is an integer from 0-3;

Y represents 6-halopyridin-3-yl, 6-(C₁-C₄)alkylpyridin-3-yl,6-(C₁-C₄)alkoxypyridin-3-yl, 2-chlorothiazol-4-yl, or3-chloroisoxazol-5-yl when n=0-3 and L represents a single bond, or Yrepresents hydrogen, C₁-C₄ alkyl, phenyl, 6-halopyridin-3-yl,6-(C₁-C₄)alkylpyridin-3-yl, 6-(C₁-C₄)alkoxypyridin-3-yl,2-chlorothiazol-4-yl, or 3-chloroisoxazol-5-yl when n=0-1 and R¹, S andL taken together represent a 5- or 6-membered ring; and

R⁴ represents C₁-C₃ alkyl.

Preferred Compounds of Formula (I) Include the Following Classes:

(1) Compounds of formula (I) wherein X is NO₂ or CN, most preferably CN.

(2) Compounds of formula (I) wherein R¹, S and L taken together form astandard 5-membered ring, n=1, and Y represents 6-chloropyridin-3-yl,i.e., having the structure

(3) Compounds of formula (I) wherein R¹, S and L taken together form astandard 5-membered ring and n=0, i.e., having the structure

(4) Compounds of formula (I) wherein R¹ represents CH₃, L represents asingle bond and Y represents 6-chloropyridin-3-yl, i.e., having thestructure

wherein n=1-3.

It will be appreciated by those skilled in the art that the mostpreferred compounds are generally those which are comprised ofcombinations of the above preferred classes.

The invention also provides new processes for preparing compounds offormula (I) as well as new compositions and methods of use, which willbe described in detail hereinafter.

DETAILED DESCRIPTION OF THE INVENTION

Throughout this document, all temperatures are given in degrees Celsius,and all percentages are weight percentages unless otherwise stated.

Unless specifically limited otherwise, the term alkyl (includingderivative terms such as alkoxy) as used herein include straight chain,branched chain, and cyclic groups. Thus, typical alkyl groups aremethyl, ethyl, 1-methylethyl, propyl, 1,1-dimethylethyl, andcyclopropyl. The term halogen includes fluorine, chlorine, bromine, andiodine.

The compounds of this invention can exist as one or more stereoisomers.The various stereoisomers include geometric isomers, diastereomers andenantiomers. Thus the compounds of the present invention include racemicmixtures, individual stereoisomers and optically active mixtures. Itwill be appreciated by those skilled in the art that one stereoisomermay be more active than the others. Individual stereoisomers andoptically active mixtures may be obtained by selective syntheticprocedures, by conventional synthetic procedures using resolved startingmaterials or by conventional resolution procedures.

The compounds of formula (Ia), wherein R¹, R², R³, R⁴, X, and Y are aspreviously defined and L is a single bond, can be prepared by themethods illustrated in Scheme A:

In step a of Scheme A, sulfide of formula (A) is oxidized withmeta-chloroperoxybenzoic acid (mCPBA) in a polar solvent below 0° C. toprovide sulfoxide of formula (B). In most cases, dichloromethane is thepreferred solvent for oxidation.

In step b of Scheme A, sulfoxide (B) is iminated with sodium azide inthe presence of concentrated sulfuric acid in an aprotic solvent underheating to provide sulfoximine of formula (C). In most cases, chloroformis the preferred solvent for this reaction.

In step c of Scheme A, the nitrogen of sulfoximine (C) can be eithercyanated with cyanogen bromide in the presence of a base, or nitratedwith nitric acid in the presence of acetic anhydride under mildlyelevated temperature, or carboxylated with alkyl (R⁴) chloroformate inthe presence of base such as 4-dimethylaminopyridine (DMAP) to provideN-substituted sulfoximine (Ia). Base is required for efficient cyanationand carboxylation and the preferred base is DMAP, whereas sulfuric acidis used as catalyst for efficient nitration reaction.

The compounds of formula (Ia), wherein X represents CN and R¹, R², R³,R⁴ and Y are as previously defined, can be prepared by the mild andefficient method illustrated in Scheme B.

In step a of Scheme B, sulfide is oxidized with iodobenzene diacetate inthe presence of cyanamide at 0° C. to give sulfilimine (F). The reactioncan be carried out in a polar aprotic solvent like CH₂Cl₂.

In step b of Scheme B, the sulfilimine (F) is oxidized with mCPBA. Abase such as potassium carbonate is employed to neutralize the acidityof mCPBA. Protic polar solvents such as ethanol and water are used toincrease the solubility of the sulfilimine starting material and thebase employed.

The α-carbon of the N-substituted sulfoximine of formula (Ia), i.e.,n=1, R³=H in the (CR²R³) group adjacent to the N-substituted sulfoximinefunction can be further alkylated or halogenated (R⁵) in the presence ofa base such as potassium hexamethyldisilamide (KHMDS) to giveN-substituted sulfoximines of formula (Ib), wherein R¹, R², R³, R⁴, X, Land Y are as previously defined and Z is an appropriate leaving group,as illustrated in Scheme C. The preferred leaving groups are iodide(R⁵=alkyl), benzenesulfonimide (R⁵=F), tetrachloroethene (R⁵=Cl), andtetrafluoroethene (R⁵=Br).

The starting sulfides (A) in Scheme A can be prepared in different waysas illustrated in Schemes D, E, F G and H.

In Scheme D, the sulfide of formula (A₁), wherein R¹, R² and Y are aspreviously defined and R³=H, can be prepared from the chloride offormula (D₁) by nucleophilic substitution with the sodium salt of analkyl thiol.

In Scheme E, the sulfide of formula (A₂), wherein R¹, R² and Y are aspreviously defined and R³=H, can be prepared from the chloride offormula (D₂) by reacting with a 2-mono substituted methyl malonate inthe presence of base such as potassium tert-butoxide to provide2,2-disubstituted malonate, hydrolysis under basic conditions to form adiacid, decarboxylation of the diacid by heating to give a monoacid,reduction of the monoacid with borane-tetrahydrofuran complex to providean alcohol, tosylation of the alcohol with toluenesulfonyl chloride(tosyl chloride) in the presence of a base like pyridine to give atosylate and replacement of the tosylate with the sodium salt of thedesired thiol.

In Scheme F, the sulfide of formula (A₃), wherein R¹, R² and Y are aspreviously defined and R³=H, can be prepared from the nitrile of formula(E) by deprotonation with a strong base and alkylation with an alkyliodide to give α-alkylated nitrile, hydrolysis of the α-alkylatednitrile in the presence of a strong acid like HCl to give an acid,reduction of the acid with borane-tetrahydrofuran complex to provide analcohol, tosylation of the alcohol with tosyl chloride in the presenceof a base like pyridine to give a tosylate and replacement of thetosylate with the sodium salt of the desired thiol.

In Scheme G, the sulfide of formula (A₄), wherein R¹, S and L takentogether form a ring, n=0, Y=isopropyl or phenyl can be prepared fromthe unsubstituted cyclic sulfide wherein m=0, 1. Chlorination of thecyclic sulfide starting material with N-chlorosuccinimide in benzenefollowed by alkylation with Grignard reagent can lead to the desiredsulfide (A₄) in satisfactory yield.

In Scheme H, the sulfide of formula (A₅), wherein R¹ is previouslydefined, L is a bond, n is 0 and Y is 6-chloropyridin-3-yl can beprepared from 2-chloro-5-bromopyridine with a halo-metal exchangefollowed by a substitution with disulfide.

Sulfoximine compounds wherein R¹, S and L taken together form asaturated 5- or 6-membered ring can also be prepared by the methodsillustrated in Scheme I wherein X and Y are as previously defined and mis 0 or 1.

In step a of Scheme I, which is similar to step b of Scheme A, sulfoxideis iminated with sodium azide in the presence of concentrated sulfuricacid or with O-mesitylsulfonylhydroxylamine in a polar aprotic solventto provide sulfoximine. Chloroform or dichloromethane are the preferredsolvents.

In step b of Scheme I, similar to step c of Scheme A, the nitrogen ofsulfoximine can be either cyanated with cyanogen bromide, or nitratedwith nitric acid followed by treatment with acetic anhydride underrefluxing conditions, or carboxylated with methyl chloroformate in thepresence of base such as DMAP to provide N-substituted cyclicsulfoximine. Base is required for efficient cyanation and carboxylationand the preferred base is DMAP, whereas sulfuric acid is used ascatalyst for efficient nitration reaction.

In step c of Scheme I, the α-carbon of N-substituted sulfoximine can bealkylated with a heteroaromatic methyl halide in the presence of a basesuch as KHMDS or butyl lithium (BuLi) to give the desired N-substitutedsulfoximines. The preferred halide can be bromide, chloride or iodide.

Alternatively, the compounds of formula (Ib) can be prepared by a firstα-alkylation of sulfoxides to give α-substituted sulfoxides and then animination of the sulfoxide followed by N-substitution of the resultingsulfoximine by using the steps c, a and b respectively as describedabove for Scheme I.

EXAMPLES Examples I-X Preparation of N-Substituted Sulfoximines ExampleI[3-(6-Chloropyridin-3-yl)-2-methylpropyl](methyl)oxido-λ⁴-sulfanylidenecyanamide(2)

A) Dimethyl 2-[(6-chloropyridin-3-yl)methyl]-2-methylmalonate

To a stirred solution of potassium tert-butoxide (4.49 g, 40 mmol) intetrahydrofuran (THF, 100 mL) was added dimethyl methylmalonate (6.43 g,44 mmol) dropwise at room temperature. After 10 min,3-chloromethyl-6-chloropyridine (6.48 g, 40 mmol) was added and theresulting mixture was stirred at room temperature overnight. The mixturewas poured into water (400 mL) and then extracted with ether (2×150 mL).The organic fractions were combined, washed with brine (100 mL) anddried over anhydrous MgSO₄. The solvent was evaporated to give a yellowoil, which was triturated with boiling hexane (2×100 mL) with the hexanebeing decanted from insoluble oil. The hexane fractions were combinedand cooled to give 6.3 g of the desired malonate derivative as a whitesolid in 58% yield: m.p. 80-81° C.

B) 2-[(6-Chloropyridin-3-yl)methyl]-2-methylmalonic acid

To a stirred solution of dimethyl2-[(6-chloropyridin-3-yl)methyl]-2-methylmalonate (10.85 g, 40 mmol) inTHF (80 mL) was added a solution of lithium hydroxide monohydrate (5.7g, 0.136 mol) in water (43 mL). The resulting mixture was stirredovernight at room temperature and then poured into water (300 mL). ThepH was adjusted to less than 2 by the addition of concentrated HCl. Theresulting mixture was extracted with ether (3×100 mL) and the etherextracts were combined, washed with brine (100 mL) and dried overanhydrous MgSO₄. After a filtration, the solvent was evaporated to give9.26 g of the product as a white solid in 95% yield: m.p. 168° C.(decomp.).

C) 3-(6-Chloropyridin-3-yl)-2-methylpropanoic acid

The solid 2-[(6-chloropyridin-3-yl)methyl]-2-methylmalonic acid (8.70 g,37.5 mmol) in a 500 mL round bottom flask was immersed in an oil bathheated to 185° C. As the solid melted carbon dioxide evolution occurred.After heating for 30 min, the reaction was deemed complete. Upon coolingthere was obtained an amber gum (6.8 g, 95% yield). [M+H]⁺=200, 202; IR:1703 (C═O). The product was about 85% pure and was used for the nextstep reaction directly.

D) 3-(6-Chloropyridin-3-yl)-2-methylpropan-1-ol

To a stirred solution of 3-(6-chloropyridin-3-yl)-2-methylpropanoic acid(6.5 g, 32.6 mmol) in THF (75 mL) cooled in an ice-water bath was addeda solution of 1 M borane in THF (48 mL, 48 mmol) in a rapid dropwisefashion. The mixture was stirred at room temperature for 4 h. Water (25mL) was added carefully followed by 2 N NaOH solution. The two phaseswere separated and the aqueous phase washed with ether (100 mL). Theorganic phases were combined, dried over anhydrous MgSO₄, filtered, andconcentrated to give 4.2 g of the product as a nearly colorless oil in69% crude yield. [M+H]⁺=186, 188; IR: 3414 (OH)

E) 3-(6-Chloropyridin-3-yl)-2-methylpropyl-4-methylbenzenesulfonate

To a stirred solution of 3-(6-chloropyridin-3-yl)-2-methylpropan-1-ol(4.0 g, 21.5 mmol) and pyridine (3.40 g, 43 mmol) in CHCl₃ (30 mL)cooled below 5° C. in an ice-water bath was added p-toluenesulfonylchloride (6.16 g, 32.3 mmol) in one portion. After 20 min, the ice-waterbath was removed and the mixture was continued to stir at roomtemperature overnight. The solution was then diluted with CH₂Cl₂ (30mL), washed with 1 N HCl (50 mL), water (50 mL), brine (50 mL), anddried over anhydrous MgSO₄. The solvent was filtered and evaporated togive 9.0 g of the crude product as a yellow oil, which was purified onsilica gel using 15% acetone in hexane (v/v) as eluent to give 5.45 g ofthe desired tosylate product as a colorless oil in 74.6% yield.[M+H]⁺=340, 342; IR: 1177 (S═O).

F) 2-Chloro-5-[2-methyl-3-(methylthio)propyl]pyridine

A solution3-(6-chloropyridin-3-yl)-2-methylpropyl-4-methyl-benzenesulfonate (5.0g, 14.7 mmol) and sodium methylthiolate (2.10 g, 30 mmol) in THF (50 mL)was stirred overnight at room temperature. The remaining unreactedstarting material indicated on TLC was converted into the productcompletely after the solution was heated at 55° C. for 4 more hours. Themixture was diluted with ether and washed with 2 N NaOH solution (50mL). The aqueous phase was washed with ether (50 mL). The combinedorganic phase was washed with brine (50 mL), dried over MgSO₄, filteredand concentrated to give 2.94 g of the desired crude sulfide in 93%yield as a yellowish oil: M⁺=215, 217; δ 2.07 (s, 3H), 0.95 (d, 3H).

G) 2-Chloro-5-[2-methyl-3-(methylsulfinyl)propyl]pyridine

To a stirred solution of2-chloro-5-[2-methyl-3-(methylthio)propyl]-pyridine (2.60 g, 12.5 mmol)in CH₂Cl₂ (35 mL) cooled to −15° C. in an ice-salt bath was addedm-chloroperoxybenzoic acid (mCPBA, ˜85%, 2.54 g, ˜12.5 mmol) portionwise at such a rate that the temperature never rose above −10° C. Afterthe addition was over, TLC showed that a single product plus a smallamount of starting material was present in the solution. To avoid anysulfone formation, the reaction was quenched at this point by theaddition of saturated NaHCO₃ (50 mL). The organic layer was separatedand the aqueous phase washed with CH₂Cl₂ (25 mL). The combined organiclayers were dried over MgSO₄ and the solvent was evaporated to give 2.66g of crude product as a yellow oil. The oil was triturated with hothexane (50 mL) and the hexane decanted after cooling. This procedureremoved most of the starting material and the resulting product (amixture of two diastereomers) was directly used for the following stepwithout further purification. [M+H]⁺=232, 234; δ 1.09 (overlapping d,3H), 2.57, 2.59 (2 s, 3H).

H) 2-Chloro-5-[2-methyl-3-(methylsulfonimidoyl)propyl]pyridine

To a stirred mixture of2-chloro-5-[2-methyl-3-(methylsulfinyl)propyl]-pyridine (2.15 g, 9.3mmol) and sodium azide (1.81 g, 28 mmol) in chloroform (30 mL) cooled inan ice-water bath was added concentrated H₂SO₄ (6 mL) and the resultingmixture stirred at this temperature for 10 min. The reaction was thenheated at 55° C. in an oil-bath for 16 hrs. Upon cooling down, themixture was diluted with ice-water (70 mL) and the organic layerremoved. The aqueous phase was washed with CH₂Cl₂ (2×30 mL) and theorganic phase was discarded. The aqueous phase was made basic by thecareful addition of aqueous ammonia whereupon an oil separated, whichwas extracted with CH₂Cl₂ (2×30 mL). The combined organic phase wasdried over MgSO₄ and solvent evaporated to give 2.15 g of the product asa yellowish oil in 94% yield. [M+H]⁺=247, 249; δ 1.11 (overlapping d,3H).

I)[3-(6-Chloropyridin-3-yl)-2-methylpropyl](methyl)oxido-λ⁴-sulfanylidenecyanamide(2)

To a stirred solution of2-chloro-5-[2-methyl-3-(methylsulfonimidoyl)-propyl]pyridine (0.432 g,1.75 mmol) and DMAP (0.24 g, 2 mmol) in CH₂Cl₂ (10 mL) was added a 3 Mcyanogen bromide solution in CH₂Cl₂ (1.2 mL, 3.5 mmol) in one portion.There was an immediate exothermic reaction accompanied by gas evolution.After stirring for 30 min at room temperature, TLC showed that all ofthe starting material had been consumed and replaced by a singleproduct. The reaction mixture was added to the top of a small pad ofsilica gel and then washed off using 7:3 hexane-acetone (v/v). Removalof the solvent gave 0.39 g of the desired N-cyanosulfoximine (2) as acolorless oil in 82% yield. [M+H]⁺=272, 274; IR: 2189 cm⁻¹.

Example II Preparation of2-chloro-5-(2-methyl-3-{methyl(oxido)[oxido-(oxo)hydrazono]-λ⁴-sulfanyl}propyl)pyridine(3)

To a stirred solution of2-chloro-5-[2-methyl-3-(methylsulfonimidoyl)-propyl]pyridine (0.432 g,1.75 mmol) (Example I-H) in CH₂Cl₂ (10 mL) cooled in an ice-water bathwas added 98% HNO₃ (0.11 g, 1.75 mmol). The nitrate salt of sulfoximineseparated from the solution. To this mixture was added acetic anhydride(4 mL) and a catalytic amount of concentrated H₂SO₄ (3 drops). Theresulting mixture was stirred at 0° C. for a few minutes and then heatedunder reflux for 1 h. During this period, the reaction mixture becamehomogeneous. To the resulting solution was added additional CH₂Cl₂ (20mL) followed by 1 N NaOH (75 mL) and the stirring was continued toquench the acetic anhydride. The organic layer was then separated andthe aqueous layer was washed with CH₂Cl₂ (80 mL). The combined organicphase was dried over MgSO₄ and solvent evaporated to give 0.49 g ofproduct (3) (yellow oil) as a 1:1 mixture of diastereomers in 96% yield.[M+H]⁺=292, 294.

Example III2-Chloro-5-(1-methyl-2-{methyl(oxido)[oxido(oxo)hydrazono]-λ⁴-sulfanyl}ethyl)pyridine(4)

A) 2-(6-Chloropyridin-3-yl)propanenitrile

To a freshly made lithium diisopropamide (LDA) (0.1 mol) solution inTHF-hexane (100 and 40 mL respectively) was added dropwise a solution of3-cyanomethyl-6-chloropyridine (14.5 g, 0.095 mol) in THF (50 mL) at−78° C. The addition was at such a rate that the reaction temperaturedid not rise above −65° C. After the addition was complete, the mixturewas stirred at this temperature for 30 min, and then slowly transferredvia canula to a cold stirred solution of iodomethane (28.38 g, 0.2 mol)in THF (100 mL) at −78° C. The rate of transfer was again at such a ratethat the reaction temperature did not rise above −65° C. After theaddition was over, the mixture was stirred at −78° C. for 30 min, thenthe temperature allowed to rise to −20° C. and the reaction was quenchedwith 2 N HCl (200 mL). Saturated sodium chloride solution (100 mL) wasadded and the phases separated. The aqueous phase was washed with ether(2×100 mL). The organic phases were combined, washed with brine anddried over Na₂SO₄. The solvent was evaporated to give a dark oil whichwas purified on silica gel using 15% acetone in hexane (v/v) to give 9.0g of the desired cyano product in 57% yield: m.p. 67-69° C. (afterrecrystallization from hexane-ether that resulted in pale yellowneedles): IR: 2242 cm⁻¹.

B) 2-(6-Chloropyridin-3-yl)propanoic acid

A stirred solution of 2-(6-chloropyridin-3-yl)propanenitrile (7.5 g, 50mmol) and concentrated hydrochloric acid (70 mL) was heated at refluxfor 3 hrs then cooled to room temperature. The solution was treated withcharcoal and then filtered through celite. The pH of the filtrate wascarefully adjusted to 4-5 by the addition of solid sodium carbonate. Theresulting mixture was extracted with CH₂Cl₂ (3×75 mL). The organicphases were combined and dried over MgSO₄ and the solvent was evaporatedto give 5.40 g of the desired acid in 65% yield as a yellow liquid whichsolidified upon standing: ¹H NMR (CDCl₃): δ 9.75 (bs, 1H, OH).

C)2-Chloro-5-(1-methyl-2-{methyl(oxido)[oxido(oxo)hydrazono]-λ⁴-sulfanyl}ethyl)pyridine(4)

The compound (4) was prepared from 2-(6-chloropyridin-3-yl)propanoicacid by a six-step procedure as described in Example I: reduction of theacid to form alcohol, tosylation of the alcohol, substitution of theresulting tosylate to sulfide, oxidation of the sulfide to sulfoxide,imination of the sulfoxide to sulfoximine, and N-nitration of thesulfoximine with nitric acid and acetic anhydride. [M+H]⁺: 278, 280; δ3.16, 3.22 (2s, diastereomeric S—CH₃).

Example IV Preparation of2-[(6-chloropyridin-3-yl)methyl]-1-oxidohexahydro-1λ⁴-thiopyran-1-ylidenecyanamide(5)

A) 1-Oxidohexahydro-1λ⁴-thiopyran-1-ylidenecyanamide (6)

Thiane-1-oxide was made by oxidation of thiane with mCPBA. The procedurewas as described above in Example I-F.

Thiane-1-imine-1-oxide was prepared by the following procedure: To asolution of freshly made O-mesitylsulfonylhydroxylamine (Johnson, C. R.;Robert A. Kirchhoff, R. A.; Corkins, H. G. J. Org. Chem. 1974, 39, 2458)(8.82 g, 41 mmol) in CH₂Cl₂ (80 mL) was added a solution ofthiane-1-oxide (2.45 g, 20 mmol) in CH₂Cl₂ (70 mL) over a period of 1.5h and the mixture was then stirred at room temperature overnight.Aqueous 10% NaOH solution (50 mL) was added to the mixture, which wasstirred at room temperature for 10 min. The organic layer was separatedand the aqueous phase was extracted with CH₂Cl₂ (50 mL). The combinedorganic layer was dried over Na₂SO₄, filtered, concentrated, andpurified on silica gel to give 0.77 g of the desired sulfoximine. Theaqueous phase that retained most of the product was extractedcontinuously with chloroform for 3 h. The chloroform solution was thendried over Na₂SO₄, filtered and concentrated to give additional 1.84 gof analytically pure product as a yellowish oil. The combined yield fromthe two procedures was 2.61 g (94%). [M+1]⁺: 134.

N-Cyano sulfoximine (6) was prepared from thiane-1-imine-1-oxide usingcyanogen bromide by the method described above in Example I-I.

B)2-[(6-Chloropyridin-3-yl)methyl]-1-oxidohexahydro-1λ⁴-thiopyran-1-ylidenecyanamide(5)

2-Chloro-5-iodomethylpyridine was first prepared by following procedure:A suspension of 2-chloro-5-chloromethylpyridine (16.2 g, 0.1 mol) andsodium idodide (22.3 g, 0.15 mol) in acetone (200 mL) was heated toreflux for 3 h and then the solvent acetone was removed by rotaryevaporator. The remaining mixture was suspended in CH₂Cl₂ and the solidwas filtered off. The filtrate was concentrated and the residue wasloaded on a silica gel column and eluted with 1:4 EtOAc-hexane to give20.8 g of 2-chloro-5-iodomethylpyridine as brown oil in 82% yield, whichturned into solid once being dried under vacuum.

To a solution of N-cyano sulfoximine (6) (0.158 g, 1.0 mmol) in THF (8mL) was added 2.5 M n-BuLi in hexane (0.44 mL, 1.1 mmol) at −78° C.After 1 h, a suspension of 2-chloro-5-iodomethylpyridine (0.28 g, 1.1mmol) in THF (3 mL) was added in one portion via a syringe. After 30min, the mixture was stirred at room temperature for 3 h. The reactionwas quenched with saturated aqueous NH₄Cl solution, extracted withCH₂Cl₂ three times, washed with brine, dried over Na₂SO₄, filtered, andconcentrated. The residue was purified on preparative reverse phase HPLCusing 55% MeCN in water as solvent to give 0.049 g of the desiredproduct in 17% yield: [M+H]⁺=284, 286.

Example V Preparation of methyl2-[(6-chloropyridin-3-yl)methyl]-1-oxidotetrahydro-1H-1λ⁴-thien-1-ylidenecarbamate(7)

A) 2-Chloro-5-[(1-oxidotetrahydrothien-2-yl)methyl]pyridine

Tetramethylene sulfoxide (6.5 g, 62 mmol) was dissolved in 30 mLanhydrous THF, stirred and cooled to −70° C. and then treated with 2.5 Mn-BuLi in hexane (24 mL, 61 mmol) over a period of 10 min. Thetemperature was raised to −20 to −30° C. (Liquid N₂/o-xylene bath) andthe mixture was stirred for a further 30 min. The mixture was cooled to−70° C. and treated dropwise with a solution of6-chloro-3-chloromethylpyridine in 15 mL THF. The reaction was stirredfor 2 h at −70° C. and then treated dropwise with trifluoroacetic acid(8.0 g, 70 mmol). The mixture was warmed to room temperature, pouredinto 75 mL water and extracted with dichloromethane (2×50 mL). Thecombined organic extracts were washed with dilute sodium bicarbonate andsaturated NaCl, dried over Na₂SO₄ and concentrated. The residue waschromatographed on silica gel with 5% methanol in dichloromethane togive 2.5 g of the desired sulfoxide as a brown oil in 35% yield.

B) 2-[(6-Chloropyridin-3-yl)methyl]tetrahydro-1H-1λ⁴-thiophen-1-imine1-oxide

2-[(6-Chloropyridin-3-yl)methyl]tetrahydro-1H-1λ⁴-thiophen-1-imine-1-oxidewas prepared from2-chloro-5-[(1-oxidotetrahydrothien-2-yl)methyl]-pyridine by the methodas described in Example I-H using NaN₃ as the iminating agent.

Separation of the two diastereomers of the sulfoximine: A crudediastereomer mixture (˜3:1 ratio of diastereomers) of the abovesulfoximine (20, 0.8 g) was added to a 4 mm silica gel plate of aChromatron® chromatographic unit. The material was eluted with a solventgradient of hexane/acetone starting with a 50:50 mixture, thenincreasing the acetone concentration in 5% increments every 200 mL. Alsoafter every 200 mL of solvent was added, then plate was partially driedbefore the next increment of solvent was added. In this manner goodseparation was achieved with only a minor amount of mixed materialseluting between the two purified diastereomers. Eluting first was theminor diastereomer which solidified upon standing. ¹³C NMR (CDCl₃):20.4, 30.0, 30.6, 54.5, 64.0, 124.2, 131.9, 139.0, 149.7, and 150.0.Eluting second was the major diastereomer (yellow gum). ¹³C NMR (CDCl₃):21.0, 30.1, 30.7, 55.9, 64.7, 124.1, 131.9, 139.3, 149.9, 150.0. Bothdiastereomers showed a [M+H]⁺ at 245 and 247.

The diastereomerically pure N-substituted sulfoximine was made from thecorrespondent diastereomeric pure sulfoximine.

C) Methyl2-[(6-chloropyridin-3-yl)methyl]-1-oxidotetrahydro-1H-1λ⁴-thien-1-ylidenecarbamate(7)

To a stirred solution of2-[(6-chloropyridin-3-yl)methyl]tetrahydro-1H-1λ⁴-thiophen-1-imine-1-oxide(diastereomeric mixture, 0.20 g, 0.82 mmol) and DMAP (0.104 g, 0.85mmol) in CH₂Cl₂ (5 mL) was added methyl chloroformate (0.077 g, 0.82mmol) in one portion and the resulting solution was stirred for 30 minat room temperature. The reaction mixture was diluted with CH₂Cl₂ (20mL), washed with 1 N HCl (20 mL) and dried over MgSO₄ and the solventevaporated to give 0.23 g of the analytically pure desired product (7)as a yellow gum in 93% yield. [M+H]⁺=303, 305.

Example VI Preparation of[1-(6-chloropyridin-3-yl)ethyl]methyl)oxido-λ⁴-sulfanylidenecyanamide(8) and[1-(6-chloropyridin-3-yl)-1-methylethyl](methyl)oxido-λ⁴-sulfanylidenecyanamide(9)

A)[(6-Chloropyridin-3-yl)methyl](methyl)oxido-λ⁴-sulfanylidene-cyanamide(10)

[(6-Chloropyridin-3-yl)methyl](methyl)oxido-λ⁴-sulfanylidene-cyanamide(10) was prepared from the corresponding sulfoximine2-chloro-5-[(methylsulfonimidoyl)methyl]pyridine by the method describedin Example I-I using cyanogen bromide as the N-cyanating agent.

2-Chloro-5-[(methylsulfonimidoyl)methyl]pyridine was prepared form thecorresponding sulfide via a two-step process as described in Example I-Gand I-H: oxidation of the sulfide to sulfoxide followed by imination ofthe sulfoxide.

B)[1-(6-Chloropyridin-3-yl)ethyl](methyl)oxido-λ⁴-sulfanylidenecyanamide(8) and[1-(6-chloropyridin-3-yl)-1-methylethyl](methyl)oxido-λ⁴-sulfanylidenecyanamide(9)

To a solution of N-cyano sulfoximine (10) (0.34 g, 1.5 mmol) andhexamethyl phosphoramide (HMPA) (0.14 mL, 0.8 mmol) in 15 mL anhydrousTHF was added dropwise a solution of 0.5 M KHMDS in toluene (3.6 mL, 1.8mmol) at −78° C. After 45 min, iodomethane (0.11 mL, 1.8 mmol) was addedin one portion via a syringe. Ten minutes later, the temperature wasallowed to rise to 0° C. After stirring for 1.5 h., the reaction wasquenched with saturated aqueous NH₄Cl, diluted with brine and extractedwith CH₂Cl₂ three times. The combined organic layer was dried overNa₂SO₄, filtered and concentrated. The residue was first purified onsilica gel twice, first time eluted with 2% MeOH in CH₂Cl₂ (v/v) and thesecond time with 9% acetone in CH₂Cl₂ (v/v) to give 0.217 g of monomethylated N-cyano sulfoximine (8) in 60% yield ([M−H]⁺=242, 244) as amixture of disastereomers and 0.066 g of dimethylated N-cyanosulfoximine (9) in 17% yield ([M−H]⁺=256, 258).

The ratio of the amount of the two compounds varied with the amount ofthe base added. In addition, the dimethylated compound (9) can also bemade from the mono-methylated molecule (8) by the same method.

Example VII Preparation of2-[(2-chloro-1,3-thiazol-5-yl)methyl]-1-oxidotetrahydro-1H-1λ⁴-thien-1-ylidenecyanamide(11)

A) 1-Oxidotetrahydro-1H-1λ⁴-thien-1-ylidenecyanamide (12)

1-Oxidotetrahydro-1H-1λ⁴-thien-1-ylidenecyanamide (12) was prepared fromtetrahydrothiophene-1-oxide by a two-step procedure as described inExample I-H and I-I: imination of the sulfoxides with sodium azide andN-cyanation of the resulting sulfoximine with cyanogen bromide. ¹³C NMR(CDCl₃): 112.3, 52.9.

B)2-[(2-Chloro-1,3-thiazol-5-yl)methyl]-1-oxidotetrahydro-1H-1λ⁴-thien-1-ylidenecyanamide

2-Chloro-5-(iodomethyl)thiazole was first prepared from2-chloro-5-chloromethylthiazole using sodium iodide as iodinating agentin acetone by the method as described in Example IV-B.

1-Oxidotetrahydro-1H-1λ⁴-thien-1-ylidenecyanamide (12) (2.0 g, 14 mmol)was dissolved in 30 mL anhydrous THF, cooled to −78° C. and treated with2.5 M n-butyl lithium in hexane (5.5 mL, 14 mmol). After 2 h at −78° C.,the anion was treated dropwise with a solution of2-chloro-5-(iodomethyl)thiazole in 10 mL anhydrous THF. After stirringfor 4 h at −78° C., the mixture was allowed to warm to 25° C. and stirfor 19 h. HPLC showed a 90% conversion of the iodide into a mixture ofthe mono and dialkylated sulfoximines. The reaction was quenched withsat. NH₄Cl solution and worked up in ethyl acetate/water. Afterevaporation of the organic phase, the residue was chromatographed bypreparative HPLC on a 50 mm×250 mm YMC AQ column with 60%acetonitrile/40% 0.1% H₃PO₄ to give the desired mono alkylated product0.32 g (7.3%) as a pale yellow oil ([M+H]⁺=276, 278).

Example VIII Preparation of(6-Ethoxypyridin-3-yl)(methyl)oxido-λ⁴-sulfanylidenecyanamide (42)

A) 2-Chloro-5-methylsulfinylpyridine

To a solution of 2-chloro-5-bromopyridine in 110 mL anhydrous etherunder nitrogen was added n-BuLi at −78° C. over a period of 5 min. Themixture was then stirred at this temperature for 1 h and methyldisulfide was added in one portion via a syringe. After 30 min, thetemperature was allowed to warm to room temperature and the reaction wascontinued for 1 h. The reaction was quenched with saturated NH₄Cl at−78° C. and half-saturated brine solution was added to the mixture.After separation of the two phases, the aqueous phase was extracted withether two more times. The combined organic layer was washed with brine,dried over Na₂SO₄, filtered, concentrated and purified on silica gelusing 20% ethyl ether in hexane as eluent to give 3.7 g of2-chloro-5-methyl-thiopyridine as a pale brownish oil in 78% yield.

2-Chloro-5-methylsulfinylpyridine was prepared by the method describedin Example I-F from 2-chloro-5-methylthiopyridine using mCPBA asoxidant.

B) 2-Ethoxy-5-(methylsulfonimidoyl)pyridine

Following the procedure as described in Example I-G using NaN₃ andconcentrated sulfuric acid as iminating agent in chloroform solventcontaining ethanol stabilizer, both sulfoximines2-chloro-5-(methylsulfonimidoyl)pyridine (m/e: [M]⁺=190, 192) and2-ethoxy-5-(methylsulfonimidoyl)pyridine (m/e: [M]⁺=200) were formed. Ifmore than one equivalent of ethanol was added into the reaction mixture,2-ethoxy-5-(methylsulfonimidoyl)pyridine was almost formed exclusively.2-Ethoxy-5-(methylsulfonimidoyl)pyridine can also be prepared from2-chloro-5-(methylsulfonimidoyl)pyridine by heating it in ethanol in thepresence of acid such as hydrogen chloride.

C) (6-Ethoxypyridin-3-yl)(methyl)oxido-λ⁴-sulfanylidenecyanamide

N-cyano 2-ethoxy sulfoximine (42) (m/e: [M]⁺=225) was prepared from2-ethoxy-5-(methylsulfonimidoyl)pyridine using cyanogen bromide asN-cyanating agent by the method described in Example I-I.

Example IX Preparation of(2-Chlorothiazole-4-yl)methyl(methyl)oxido-λ⁴-sulfanylidenecyanamide(43)

A) (2-Chlorothiazole-4-yl)methyl(methyl)oxido-λ⁴-sulfinylidenecyanamide

To a stirred solution of the 2-chloro-4-methylthiomethylthiazole (1.79g, 10 mmol) and cyanamide (0.84 g, 20 mmol) in CH₂Cl₂ (30 mL) cooled to0° C. was added iodobenzene diacetate in one portion and the resultingmixture was stirred at 0° C. for 1 h. The reaction was quenched withsodium bisulfite solution. The organic phase was separated and theaqueous phase extracted with CH₂Cl₂ one more time. The combined organiclayer was dried over Na₂SO₄, filtered, concentrated, and purified onsilica gel using 60% acetone in hexane to give 1.62 g of the product asa white crystalline solid in 74% yield. m.p. 106-108° C.

B) (2-Chlorothiazole-4-yl)methyl(methyl)oxido-λ⁴-sulfanylidenecyanamide(43)

To a stirred solution of the 80% 3-chloroperoxybenzoic acid (2.1 g, 9.8mmol) in ethanol (25 mL) cooled to 0° C. was added a solution ofpotassium carbonate (2.7 g, 19.6 mmol) in water (15 mL). The resultingmixture was stirred at 0° C. for 20 min. Then a solution of thesulfilimine starting material (1.43, 6.5 mmol) in ethanol (20 mL) wasadded at once. The resulting mixture was stirred for 40 min at 0° C. andsaturated sodium bisulfite was added to quench the excess peracid. Mostof the solvent was evaporated and water was added to the residue. Theinsoluble solid was filtered, washed with several portions of water, andthen dried under vacuum to give 1.02 g of the desired sulfoximineproduct as a white crystalline solid in 65% yield, m.p. 113-114° C.

Example X Preparation of(1-oxido-2-phenyltetrahydro-1H-11⁴-thien-1-ylidene)cyanamide (22)

A) (2-phenyltetrahydro-1H-11⁴-thien-1-ylidene)cyanamide

To a stirred mixture of 2-phenyltetrahydrothiophene (prepared fromtetrahydrothiophene by the method described in Scheme G) (0.82 g, 0.005mol) and cyanamide (0.42 g, 0.01 mol) in CH₂Cl₂ (20 mL) cooled to 0° C.was added iodobenzene diacetate (3.22 g, 0.01 mol) in one portion. Theresulting solution was stirred at 0° C. for 30 min followed by roomtemperature for 30 min. Water (30 mL) was added to the red reactionmixture and the organic phase separated. The aqueous phase was extractedwith CH₂Cl₂ and the combined organic phases were dried (MgSO₄) and thesolvent evaporated. The red reside was chromatographed on a silica gelcolumn and eluted with 1:1 hexanes-acetone to give 0.57 g (56%) of thedesired compound as an orange gum.

B) (1-oxido-2-phenyltetrahydro-1H-11⁴-thien-1-ylidene)cyanamide (22)

To a solution of 3-chloroperoxybenzoic acid (0.41 g, 0.0024 mol) in 95%EtOH (4 mL) cooled to 0° C. was added a solution of K₂CO₃ (0.66 g,0.0048 mol) in water (3 mL). The resulting mixture was stirred for 20min at 0° C. then a solution of(2-phenyltetrahydro-1H-11⁴-thien-1-ylidene)cyanamide (0.25 g, 0.0012mol) in 95% EtOH (10 mL) was added in one portion. The ice bath wasremoved and stirring was continued for 1 hr. Most of the solvent wasremoved in vacuo and water (10 mL) was added. The remaining3-chloroperoxybenzoic acid was quenched by addition of sodium bisulfiteand the pH adjusted to ˜12 by the addition of 50% NaOH. The resultingmixture was extracted with CH₂Cl₂ (2×30 mL). The organic fractions werecombined, dried (MgSO₄) and the solvent evaporated to give the titlecompound as a clear oil (0.21 g, 80%) which did not require furtherpurification. ¹H NMR analysis was consistent with the compound being a56:44 mixture of diastereomers.

Table 1 summarizes those compounds prepared in Examples I-X as well aslists other compounds of the invention prepared according to theprocedures described above.

TABLE 1 Comp # Structure Characterization 2

[M + H]⁺: 272, 274; IR: 2189 cm⁻¹ 3

[M + H]⁺: 292, 294 4

[M + H]⁺: 278, 280 5

[M + H]⁺: 284, 286 6

[M − H]⁺: 159 7

[M + H]⁺: 303, 305 8

[M − H]⁺: 242, 244 9

[M − H]⁺: 256, 258 10

[M − H]⁺: 228 11

[M + H]⁺: 276, 278 12

¹³C NMR (CDCl₃): δ112.3, 52.9 13

[M + H]⁺: 244, 246; IR: 2180 cm⁻¹ 14

[M − H]⁺: 268, 270 15

[M + H]⁺: 258, 260; IR: 2188 cm⁻¹ 16

[M + H]⁺: 272, 274; IR: 2189 cm⁻¹ 17

[M + H]⁺: 272, 274; IR: 2192 cm⁻¹ 18

[M + H]⁺: 258, 260; δ 7.90 (dd, 1H) 19

[M + H]⁺: 258, 260; δ 7.86 (dd, 1H) 20

[M + H]⁺: 270, 272; ¹³C NMR (CDCl₃): δ 20.14 21

[M + H]⁺: 270, 272; ¹³C NMR (CDCl₃): δ 21.16 22

[M + H]⁺: 221; IR: 2192 cm⁻¹ 23

¹H NMR (CDCl₃): δ 7.05, 6.92 (2 s, 1H, diastereomers) 24

¹H NMR (CDCl₃): δ 6.42, 6.34 (2 s, 1H, diastereomers) 25

[M + H]⁺: 248, 250 26

[M − H]⁺: 256, 258 27

[M − H]⁺: 318, 320 28

[M − H]⁺: 242, 244; ¹H NMR (DMSO): δ 3.419 (s, 3H) 29

[M − H]⁺: 242, 244; ¹H NMR (DMSO): δ 3.406 (s, 3H) 30

[M − H]⁺: 248 31

[M + H]⁺: 187; IR: 2192 cm⁻¹ 32

[M + H]⁺: 187; IR: 2188 cm⁻¹ 33

[M − H]⁺: 250, 252 34

¹³C NMR (CDCl₃): δ52.3, 24.0 35

¹³C NMR (CDCl₃): δ66.29, 63.85 36

[M + H]⁺: 264, 266 37

[M + H]⁺: 264, 266 38

[M + H]⁺: 292, 294 39

[M + H]⁺: 278, 280; ¹H NMR: δ 4.92 (q, 1H) 40

[M + H]⁺: 278, 280; ¹H NMR: δ 5.10 (q, 1H) 41

[M + H]⁺: 290, 292; ¹³C NMR: δ 66.41 42

[M]⁺: 225 43

[M + H]⁺: 236

Example IX Insecticidal Testing

The compounds identified in Table 2 were prepared using the proceduresillustrated in the foregoing examples, and the compounds were testedagainst cotton aphid, green peach aphid, corn earworm, beet armyworm,fruit fly, mosquito, sweet potato whitefly and Colorado potato beetleusing procedures described hereinafter.

TABLE 2 Comp CA CA CEW BAW BAW FF FF YFM SPW CPB # 200 50 50 50 SYM SYM25 26 200 50 2 A B G G G G G G H H 3 B G G G G G G G H H 4 F G G G F G GG H H 5 A A G G E G G E H H 6 G G G G G G G G H H 7 B G G G G G G G H H8 A A G G E A A A A A 9 A A G G F A C A H H 10 A A G G F A A A A B 11 AA G G D G D A H H 12 A A D F A A D G B H 13 A A G G F G G G A H 14 A A GG G G F A H H 15 A B G G G G G G H H 16 A A G G F G G G H H 17 A A G G GG G G H H 18 A A G G F G G G B H 19 A A G G G G F G C H 20 A A G G B F FA A A 21 A A G G G G G B H H 22 A B G G F G G G H H 23 A A G G F A A A HH 24 A A G G F F A A H H 25 A A G G G B C A H H 26 A A G G F A A A H H27 A A G G G G G B H H 28 A A G G D A A A A H 29 A A G G A A A A A H 30A A G G G G G G H H 31 A G G G G G G G H H 32 B G G G E G G G H H 33 A AG G G F F G G H 34 A A G G F G F G G H 35 A A G G F D F B A B 36 A A G GG F F G G H 37 A A G G G G G G H H 38 A B G G G G G F H H 39 A G G G G GF G H H 40 B G G G G G G G H H 41 A A G G G G F A A A 42 A C G G G G G GH H 43 B C G G G F F G H H CA 200 refers to % control at 200 ppm againstcotton aphid in foliar spray tests, CA 50 refers to % control at 50 ppmagainst cotton aphid in foliar spray tests, CEW 50 refers to % mortalityat 50 μg/cm2 against corn earworm in dietary tests, BAW 50 refers to %mortality at 50 μg/cm2 against beet armyworm in dietary tests, BAW SYMrefers to % showing intoxicated symptoms at 10 μg/larva against beetarmyworm in injection tests, FF SYM refers to % showing intoxicatedsymptoms at 25 μg/cm2 against fruit fly in dietary tests, FF 25 refersto % mortality at 25 μg/cm2 against fruit fly in dietary tests, YFM 26refers to % control at 26 ppm against yellow fever mosquito in submergetests, SPW 200 refers to % control at 200 ppm against sweet potatowhitefly in foliar spray tests, CPB 50 refers to % control at 50 ppmagainst Colorado potato beetle in foliar spray tests.

In each case of Table 2 the rating scale is as follows:

% Control (or Mortality) Rating  90-100 A 80-89 B 70-79 C 60-69 D 50-59E Less than 50 F Inactive G Not tested H

The compounds that showed high activities against cotton aphid in Table2 were further tested with multiple lower doses (rundown assays) againstcotton aphid using procedures described hereinafter. Results are shownin Table 3.

TABLE 3 Comp % Control at ppm, against cotton aphid # 0.012 0.049 0.1950.78 3.12 12.5 50 20 H B A A A A A 41 H C A A A A A 12 H H G E E A A 34H C B B A A A 36 H F F C A A A 13 H G F A A A A 28 A A A A A H H 29 A AA A A H H

In each case of Table 3 the rating scale is the same as that used forTable 2.

The compounds that showed high activities against cotton aphid in Table2 were further tested in rundown assays against green peach aphid usingprocedures described hereinafter. Results are shown in Table 4.

TABLE 4 Comp % Control at ppm, against green peach aphid # 0.012 0.0490.195 0.78 3.12 12.5 50 20 H F F F F A A 41 H F F E D A A 12 H H G G G FF 34 H F F E D D D 36 H F E D C A A 13 H G G F C C B 28 F F B A A H H 29F D A A A H H

In each case of Table 4 the rating scale is the same as that used forTable 2.

The compounds that showed high activities against sweet potato whiteflyin Table 2 were further tested in rundown assays against sweet potatowhitefly using procedures described hereinafter. Results are shown inTable 5.

TABLE 5 % Control at ppm, against sweet potato whitefly Comp # 0.4-0.782-3.13 10-12.5 50 10 F D A A 20 F F A A 8 A A A A 28 A A A A 29 A A A A

In each case of Table 5 the rating scale is the same as that used forTable 2.

The compounds that showed high activities against Colorado potato beetlein Table 2 were further tested in rundown assays against Colorado potatobeetle using procedures described hereinafter. Results are shown inTable 6.

TABLE 6 % Control at ppm, against Colorado potato beetle Comp # 0.783.13 12.5 50 20 F F A A 41 F F D A 10 H G E B 8 H D A A

In each case of Table 6 the rating scale is the same as that used forTable 2.

Insecticidal Test for Cotton Aphid (Aphis gossypii).

Squash with fully expanded cotyledon leaves were trimmed to onecotyledon per plant and infested with cotton aphid (wingless adult andnymph) 1 day prior to chemical application. Each plant is examinedbefore chemical application to ensure proper infestation (ca. 30-70aphids per plant). Compounds (3 mg) were dissolved in 3 mL ofacetone:methanol (50:50) solvent, forming stock solutions of 1000 ppm.The stock solutions were then diluted with 0.025% Tween 20 (in H₂O) tomake 200 and 50 ppm spray solutions. A hand-held Devilbiss sprayer wasused to apply the spray solutions until runoff to both sides of thesquash cotyledon leaves. Four plants (4 replications) were used for eachconcentration of each compound. Reference plants (solvent check) weresprayed with 0.025% Tween 20 only. Treated plants were held in a holdingroom for 3 days at approximately 23° C. and 40% RH before the number oflive aphids on each plant was recorded. Insecticidal activity wasmeasured by Corrected % Control using Abbott's correction formula andpresented in Table 2:Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live aphids on solvent check plants        -   Y=No. of live aphids on treated plants

Compounds that showed high activity (high Corrected % Control) from theabove basic screening were further assayed in rundown assays using thesame procedures with 0.012, 0.049, 0.195, 0.78, 3.13, 12.5 and/or 50 ppmas test doses. The Corrected % Control values from these rundown assaysare given in Table 3.

Insecticidal Test for Green Peach Aphid (Myzus persicae).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 green peach aphids (wingless adult and nymph) 2-3 days prior tochemical application. Four seedlings were used for each treatment. Fivemilligrams of test compounds were dissolved in 5 mL of acetone:methanol(50:50) solvent. The solutions were then diluted with 0.025% Tween 20(in H₂O) to make 0.012, 0.049, 0.195, 0.78, 3.13, 12.5 and/or 50 ppmspray solutions. A hand-held Devilbiss sprayer was used for spraying asolution to both sides of cabbage leaves until runoff. Reference plants(solvent check) were sprayed with 0.025% Tween 20 only. Treated plantswere held in a holding room for three days at approximately 23° C. and40% RH prior to grading. Evaluation was conducted by counting the numberof live aphids per plant under a microscope. Insecticidal activity wasmeasured by using Abbott's correction formula:Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live aphids on solvent check plants        -   Y=No. of live aphids on treated plants

The Corrected % Control values from these rundown assays are given inTable 4.

Insecticidal Test for Corn Earworm (Helicoverpa zea) and Beet Armyworm(Spodoptera exigua) in Dietary Assays.

Dietary assays were conducted in 128-well plastic trays. To prepare testsolution, the test compound was formulated at 2000 ppm in 2 mL ofacetone:water (9:1). A volume of 50 μl of the test solutions waspipetted upon the surface of 1 mL of lepidopteran diet (SouthlandMulti-Species Lepidopteran Diet) in each well of 128-well plastic trays.Eight wells (8 replications) were used for each treatment on each insectspecies. This application rate was equivalent to 50 μg/cm². Asecond-instar corn earworm or beet armyworm larva was placed upon thetreated diet in each well once the solvent had been air-dried. Trayscontaining the treated diet and larvae were covered with self-adhesivetransparent sheets and held in a growth chamber at 25° C., 50-55% RH,and 16 h light: 8 h dark Observation were conducted 5 days aftertreatment and infestation. The number of dead insects is converted to %mortality that is given in Table 2.% Mortality=100*X/Y

-   -   where X=No. of dead insects        -   Y=Total No. of insects tested (=8)            Insecticidal Test for Beet Armyworm (Spodoptera exigua) in            Injection Assays.

Test solutions were prepared by dissolving 2 mg of tech grade compoundin 100 μl of dimethyl sulfoxide or acetone. Each 4^(th) instar beetarmyworm larva was injected with 0.5 μl (10 μg of test compound perlarva) solution using a Hamilton 10 μl 33½ gauge syringe. The testsolution was injected into the abdomen of a larva, just underneath thecuticle and with the long axis of the syringe needle parallel to thelong axis of the insect's body. A solvent blank and an untreated platewere included to each test to ensure validity. Six larvae were used foreach treatment. Injected larvae were individually placed in the wells of6-well polystyrene plates with a small amount of lepidopteran diet(Southland Multi-Species Lepidopteran Diet). Plates were held at roomtemperature in the lab and were graded at 1, 24, and 48 h. Intoxicatedsymptoms were observed at each time point. The number of larvae showingsymptoms was converted to % Show Symptoms.% Show Symptoms=100*X/Y

-   -   where X=No. of larvae showing symptoms        -   Y=Total No. of larvae tested (=6)            The results (% Show Symptom) from the 1 h observation are            presented in Table 2.            Insecticidal Test for Fruit Fly (Drosophila melanogaster).

Polystyrene plates with 24 wells were filled with approximately 300 μlof an agar solution containing 20 g of agar in 1000 mL of 10% sucrosesolution. Green or yellow food coloring was added to the agar solutionas the color will be visible in the abdomen of the fly when ingested(providing an indication of ingestion observation). Prior to treatment,1.5-cm filter paper disks were individually placed on the top of thesolidified agar layer in the wells. Test solutions were prepared byadding 500 μl of acetone:water (2:1) solvent to 2 mg of tech gradecompounds, then adding an additional 500 μl of 10% sucrose solution toprovide final concentration of 2000 ppm. For the solvent blank, 500 μlof acetone:water (2:1) solvent was added to 500 μl of 10% sucrosesolution. A volume of 25 μl of the formulated 2000 ppm solution waspipetted onto the filter paper in each well (equivalent to 25 μg/cm²).Four wells (4 replications) were used for each compound. Plates werethen placed in a fume hood for 30-45 minutes to allow solvent toevaporate. Test flies were placed in a refrigerator for 10-15 minutesand transferred onto a glass dish that was kept on ice. Chilled flieswere transferred to the treated plates with a camel's hair brush. Onaverage, 5-8 flies were used for each well. The plates were covered withlids immediately after the infestation and held at room temperature inthe laboratory. Observation for intoxicated symptoms was conducted at 4h and % mortality was recorded at 48 h. The number of flies showingsymptoms was converted to % Show Symptoms and the number of dead flieswas converted to % Mortality.% Show Symptoms=100*X/Y

-   -   where X=No. of flies showing symptoms        -   Y=Total No. of flies tested            % Mortality=100*X/Y    -   where X=No. of dead flies        -   Y=Total No. of flies tested            Results are presented in Table 2.            Insecticidal Test for Mosquito (Aedes aegypd).

This test was designed to evaluate the insecticidal activity ofcompounds against yellow fever mosquito larvae through contact andingestion. Micro-titer plates with 96 wells were treated with formulatedcompounds in dimethyl sulfoxide at 4000 ppm concentration. A Tomtecrobotic system was used to dispense 1.5 μl of each formulatedexperimental solution into each well of the plates. Each compound wasapplied to 6 wells (6 replications). Subsequent to application, mosquitolarvae (3 hours old following hatch) were suspended in water containing0.4% mosquito diet (brewers yeast:liver powder=1:3) and transferred tothe wells. A Labsystems Multidrop robotic system was used to dispensealiquots of 230 μl of this aqueous solution with 5-8 mosquito larvaeinto each well of the treated plates. The final test concentration wasapproximately 26 ppm. After infestation, the plates were covered with amatching clear plastic lid that allows moisture to escape. Infestedplates were held in an incubator at 22° C. for 72 h before they wereexamined under a microscope. Insecticidal activity was recorded for eachreplication as 100% control (all dead) or 0% control (no effect).Results are presented in Table 2.

Insecticidal Test for Sweet Potato Whitefly (Bemisia tabaci).

This test was designed to measure the capability of whitefly eggs and/oryoung nymphs to develop to large nymphs. Cotton seedlings at the growthstage of one or two expanding true leaf were trimmed so that only thefirst true leaf remained (cotyledon leaves were also removed). Theplants were pre-infested with sweet potato whitefly eggs by keepingplants next to the colony-keeping plants for two or three days. Theinfested plants were carefully checked for presence of similar eggdensity before use in the insecticidal tests. Master solutions of testcompounds at 2000 ppm were prepared in acetone:water (9:1). The 200 ppmspray solutions were then made by diluting 1 mL of the master solutionwith 9 mL of 0.025% Tween 20 (in water). The test solutions were sprayedwith a hand-held Devilbiss sprayer until runoff to both sides of theinfested cotton leaves. Four plants (4 replications) were used for eachcompound. Reference plants (solvent check) were sprayed with 0.025%Tween 20 containing 9% acetone. Treated plants were held in a holdingroom for 13 or 14 days at approximately 23° C. and 40% RH beforeevaluation. To evaluate the efficacy of the compounds, the number oflive large nymphs in an area of 1 square inch on the lower surface ofthe treated cotton leaves was counted under a microscope. Insecticidalactivity is determined by Corrected % Control using Abbott's correctionformula and presented in Table 2:Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live large nymphs on solvent check plants        -   Y=No. of live large nymphs on treated plants

Compounds that showed high activity (high Corrected % Control) from theabove basic screening were further tested in rundown assays using thesame procedures with test doses ranging from 0.4 ppm to 50 ppm. TheCorrected % Control values from these rundown assays are given in Table5.

Insecticidal Test for Colorado Potato Beetle (Leptinotarsadecemlineata).

Tomato seedlings at the growth stage of three or four expanding leaveswere used. Master solutions of test compounds at 2000 ppm were preparedin acetone:water (9:1). The 50 ppm spray solutions were made by diluting0.5 mL of the master solution with 18.5 mL of 0.025% Tween 20 (inwater). The test solutions were sprayed with a hand-held Devilbisssprayer until runoff to all surfaces of the plants. Four plants (4replications) were used for each treatment. Reference plants (solventcheck) were sprayed with 0.025% Tween 20 containing 2.25% acetone.Treated plants were held in the laboratory for approximately 3 h toallow drying before the upper portion (with two or three leaves) of aplant was cut and placed in a 10×2.5-cm petri dish containingapproximately 10 mL of solidified 1% agar at the bottom. Five 2^(nd) or3^(rd) instar larvae were placed on the treated plant tissue, and thepetri dishes were covered and held in an incubator at 25° C. At 5 daysfollowing treatment, insecticidal activity was evaluated by counting thenumber of live larvae in each dish. Corrected % Control is calculatedusing Abbott's correction formula and presented in Table 2:Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live larvae on solvent check plants        -   Y=No. of live larvae on treated plants

Compounds that showed high activity (high Corrected % Control) from theabove basic screening were further tested in rundown assays using thesame procedures with test doses ranging from 0.78 ppm to 50 ppm. TheCorrected % Control values from these rundown assays are given in Table6.

Insecticide Utility

The compounds of the invention are useful for the control of insects.Therefore, the present invention also is directed to a method forinhibiting an insect which comprises applying to a locus of the insectan insect-inhibiting amount of a compound of formula (I).

The “locus” of insects is a term used herein to refer to the environmentin which the insects live or where their eggs are present, including theair surrounding them, the food they eat, or objects which they contact.For example, insects which eat or contact edible or ornamental plantscan be controlled by applying the active compound to plant parts such asthe seed, seedling, or cutting which is planted, the leaves, stems,fruits, grain, or roots, or to the soil in which the roots are growing.It is contemplated that the compounds might also be useful to protecttextiles, paper, stored grain, seeds, domesticated animals, buildings orhuman beings by applying an active compound to or near such objects. Theterm “inhibiting an insect” refers to a decrease in the numbers ofliving insects, or a decrease in the number of viable insect eggs. Theextent of reduction accomplished by a compound depends, of course, uponthe application rate of the compound, the particular compound used, andthe target insect species. At least an inactivating amount should beused. The terms “insect-inactivating amount” are used to describe theamount, which is sufficient to cause a measurable reduction in thetreated insect population. Generally an amount in the range from about 1to about 1000 ppm by weight active compound is used. For example,insects which can be inhibited include, but are not limited to:

Lepidoptera—Heliothis spp., Helicoverpa spp., Spodoptera spp., Mythimnaunipuncta, Agrotis ipsilon, Earias spp., Euxoa auxiliaris, Trichoplusiani, Anticarsia gemmatalis, Rachiplusia nu, Plutella xylostella, Chilospp., Scirpophaga incertulas, Sesamia inferens, Cnaphalocrocismedinalis, Ostrinia nubilalis, Cydia pomonella, Carposina niponensis,Adoxophyes orana, Archips argyrospilus, Pandemis heparana, Epinotiaaporema, Eupoecilia ambiguella, Lobesia botrana, Polychrosis viteana,Pectinophora gossypiella, Pieris rapae, Phyllonorycter spp., Leucopteramalifoliella, Phyllocnisitis citrellaColeoptera—Diabrotica spp., Leptinotarsa decemlineata, Oulema oryzae,Anthonomus grandis, Lissorhoptrus oryzophilus, Agriotes spp., Melanotuscommunis, Popillia japonica, Cyclocephala spp., Tribolium spp.Homoptera—Aphis spp., Myzus persicae, Rhopalosiphum spp., Dysaphisplantaginea, Toxoptera spp., Macrosiphum euphorbiae, Aulacorthum solani,Sitobion avenae, Metopolophium dirhodum, Schizaphis graminum,Brachycolus noxius, Nephotettix spp., Nilaparvata lugens, Sogatellafurcifera, Laodelphax striatellus, Bemisia tabaci, Trialeurodesvaporariorum, Aleurodes proletella, Aleurothrixus floccosus,Quadraspidiotus perniciosus, Unaspis yanonensis, Ceroplastes rubens,Aonidiella aurantiiHemiptera—Lygus spp., Eurygaster maura, Nezara viridula, Piezodorusguildingi, Leptocorisa varicornisThysanoptera—Frankliniella occidentalis, Thrips spp., ScirtothripsdorsalisIsoptera—Reticulitermes flavipes, Coptotermes formosanusOrthoptera—Blattella germanica, Blatta orientalis, Gryllotalpa spp.Diptera—Liriomyza spp., Musca domestica, Aedes spp., Culex spp.,Anopheles spp.Hymenoptera—Iridomyrmex humilis, Solenopsis spp., Monomorium pharaonic,Atta spp., Pogonomyrmex spp., Camponotus spp.Siphonaptera—Ctenophalides spp., Pulex irritansAcarina—Tetranychus spp., Panonychus spp., Eotetranychus carpini,Phyllocoptruta oleivora, Aculus pelekassi, Brevipalpus phoenicis,Boophilus spp., Dermacentor variabilis, Rhipicephalus sanguineus,Amblyomma americanum, Ixodes spp., Notoedres cati, Sarcoptes scabiei,Dermatophagoides spp.Compositions

The compounds of this invention are applied in the form of compositionswhich are important embodiments of the invention, and which comprise acompound of this invention and a phytologically-acceptable inertcarrier. The compositions are either concentrated formulations which aredispersed in water for application, or are dust or granular formulationswhich are applied without further treatment. The compositions areprepared according to procedures and formulae which are conventional inthe agricultural chemical art, but which are novel and important becauseof the presence therein of the compounds of this invention. Somedescription of the formulation of the compositions will be given,however, to assure that agricultural chemists can readily prepare anydesired composition.

The dispersions in which the compounds are applied are most oftenaqueous suspensions or emulsions prepared from concentrated formulationsof the compounds. Such water-soluble, water-suspendable or emulsifiableformulations are either solids, usually known as wettable powders, orliquids usually known as emulsifiable concentrates or aqueoussuspensions. Wettable powders, which may be compacted to form waterdispersible granules, comprise an intimate mixture of the activecompound, an inert carrier, and surfactants. The concentration of theactive compound is usually from about 10% to about 90% by weight. Theinert carrier is usually chosen from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among the sulfonated lignins, thecondensed naphthalenesulfonates, the naphthalenesulfonates, thealkylbenzenesulfonates, the alkyl sulfates, and nonionic surfactantssuch as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of the compounds comprise a convenientconcentration of a compound, such as from about 50 to about 500 gramsper liter of liquid, equivalent to about 10% to about 50%, dissolved inan inert carrier which is either a water miscible solvent or a mixtureof water-immiscible organic solvent and emulsifiers. Useful organicsolvents include aromatics, especially the xylenes, and the petroleumfractions, especially the high-boiling naphthalenic and olefinicportions of petroleum such as heavy aromatic naphtha. Other organicsolvents may also be used, such as the terpenic solvents including rosinderivatives, aliphatic ketones such as cyclohexanone, and complexalcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiableconcentrates are chosen from conventional nonionic surfactants, such asthose discussed above.

Aqueous suspensions comprise suspensions of water-insoluble compounds ofthis invention, dispersed in an aqueous vehicle at a concentration inthe range from about 5% to about 50% by weight. Suspensions are preparedby finely grinding the compound, and vigorously mixing it into a vehiclecomprised of water and surfactants chosen from the same types discussedabove. Inert ingredients, such as inorganic salts and synthetic ornatural gums, may also be added, to increase the density and viscosityof the aqueous vehicle. It is often most effective to grind and mix thecompound at the same time by preparing the aqueous mixture, andhomogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

The compounds may also be applied as granular compositions, which areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the compound,dispersed in an inert carrier which consists entirely or in large partof clay or a similar inexpensive substance. Such compositions areusually prepared by dissolving the compound in a suitable solvent andapplying it to a granular carrier which has been pre-formed to theappropriate particle size, in the range of from about 0.5 to 3 mm. Suchcompositions may also be formulated by making a dough or paste of thecarrier and compound and crushing and drying to obtain the desiredgranular particle size.

Dusts containing the compounds are prepared simply by intimately mixingthe compound in powdered form with a suitable dusty agriculturalcarrier, such as kaolin clay, ground volcanic rock, and the like. Dustscan suitably contain from about 1% to about 10% of the compound.

It is equally practical, when desirable for any reason, to apply thecompound in the form of a solution in an appropriate organic solvent,usually a bland petroleum oil, such as the spray oils, which are widelyused in agricultural chemistry.

Insecticides and acaricides are generally applied in the form of adispersion of the active ingredient in a liquid carrier. It isconventional to refer to application rates in terms of the concentrationof active ingredient in the carrier. The most widely used carrier iswater.

The compounds of the invention can also be applied in the form of anaerosol composition. In such compositions the active compound isdissolved or dispersed in an inert carrier, which is apressure-generating propellant mixture. The aerosol composition ispackaged in a container from which the mixture is dispensed through anatomizing valve. Propellant mixtures comprise either low-boilinghalocarbons, which may be mixed with organic solvents, or aqueoussuspensions pressurized with inert gases or gaseous hydrocarbons.

The actual amount of compound to be applied to loci of insects and mitesis not critical and can readily be determined by those skilled in theart in view of the examples above. In general, concentrations from 10ppm to 5000 ppm by weight of compound are expected to provide goodcontrol. With many of the compounds, concentrations from 100 to 1500 ppmwill suffice.

The locus to which a compound is applied can be any locus inhabited byan insect or mite, for example, vegetable crops, fruit and nut trees,grape vines, ornamental plants, domesticated animals, the interior orexterior surfaces of buildings, and the soil around buildings.

Because of the unique ability of insect eggs to resist toxicant action,repeated applications may be desirable to control newly emerged larvae,as is true of other known insecticides and acaricides.

The compounds of the present invention (Formula I) are often applied inconjunction with one or more other insecticides or fungicides to obtaincontrol of a wider variety of pests and diseases. When used inconjunction with other insecticides or fungicides, the presently claimedcompounds can be formulated with the other insecticides or fungicides,tank mixed with the other insecticides or fungicides, or appliedsequentially with the other insecticides or fungicides.

Some of the insecticides that can be employed beneficially incombination with the compounds of the present invention include:antibiotic insecticides such as allosamidin and thuringiensin;macrocyclic lactone insecticides such as spinosad; avermectininsecticides such as abamectin, doramectin, emamectin, eprinomectin,ivermectin and selamectin; milbemycin insecticides such as lepimectin,milbemectin, milbemycin oxime and moxidectin; arsenical insecticidessuch as calcium arsenate, copper acetoarsenite, copper arsenate, leadarsenate, potassium arsenite and sodium arsenite; botanical insecticidessuch as anabasine, azadirachtin, d-limonene, nicotine, pyrethrins,cinerins, cinerin I, cinerin II, jasmolin I, jasmolin II, pyrethrin I,pyrethrin II, quassia, rotenone, ryania and sabadilla; carbamateinsecticides such as bendiocarb and carbaryl; benzofuranylmethylcarbamate insecticides such as benfuracarb, carbofuran,carbosulfan, decarbofuran and furathiocarb; dimethylcarbamateinsecticides dimitan, dimetilan, hyquincarb and pirimicarb; oximecarbamate insecticides such as alanycarb, aldicarb, aldoxycarb,butocarboxim, butoxycarboxim, methomyl, nitrilacarb, oxamyl, tazimcarb,thiocarboxime, thiodicarb and thiofanox; phenyl methylcarbamateinsecticides such as allyxycarb, aminocarb, bufencarb, butacarb,carbanolate, cloethocarb, dicresyl, dioxacarb, EMPC, ethiofencarb,fenethacarb, fenobucarb, isoprocarb, methiocarb, metolcarb, mexacarbate,promacyl, promecarb, propoxur, trimethacarb, XMC and xylylcarb;dinitrophenol insecticides such as dinex, dinoprop, dinosam and DNOC;fluorine insecticides such as barium hexafluorosilicate, cryolite,sodium fluoride, sodium hexafluorosilicate and sulfluramid; formamidineinsecticides such as amitraz, chlordimeform, formetanate andformparanate; fumigant insecticides such as acrylonitrile, carbondisulfide, carbon tetrachloride, chloroform, chloropicrin,para-dichlorobenzene, 1,2-dichloropropane, ethyl formate, ethylenedibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide,iodomethane, methyl bromide, methylchloroform, methylene chloride,naphthalene, phosphine, sulfuryl fluoride and tetrachloroethane;inorganic insecticides such as borax, calcium polysulfide, copperoleate, mercurous chloride, potassium thiocyanate and sodiumthiocyanate; chitin synthesis inhibitors such as bistrifluoron,buprofezin, chlorfluazuron, cyromazine, diflubenzuron, flucycloxuron,flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron,penfluoron, teflubenzuron and triflumuron; juvenile hormone mimics suchas epofenonane, fenoxycarb, hydroprene, kinoprene, methoprene,pyriproxyfen and triprene; juvenile hormones such as juvenile hormone I,juvenile hormone II and juvenile hormone III; moulting hormone agonistssuch as chromafenozide, halofenozide, methoxyfenozide and tebufenozide;moulting hormones such as α-ecdysone and ecdysterone; moultinginhibitors such as diofenolan; precocenes such as precocene I, precoceneII and precocene III; unclassified insect growth regulators such asdicyclanil; nereistoxin analogue insecticides such as bensultap, cartap,thiocyclam and thiosultap; nicotinoid insecticides such as flonicamid;nitroguanidine insecticides such as clothianidin, dinotefuran,imidacloprid and thiamethoxam; nitromethylene insecticides such asnitenpyram and nithiazine; pyridylmethylamine insecticides such asacetamiprid, imidacloprid, nitenpyram and thiacloprid; organochlorineinsecticides such as bromo-DDT, camphechlor, DDT, pp′-DDT, ethyl-DDD,HCH, gamma-HCH, lindane, methoxychlor, pentachlorophenol and TDE;cyclodiene insecticides such as aldrin, bromocyclen, chlorbicyclen,chlordane, chlordecone, dieldrin, dilor, endosulfan, endrin, HEOD,heptachlor, HHDN, isobenzan, isodrin, kelevan and mirex; organophosphateinsecticides such as bromfenvinfos, chlorfenvinphos, crotoxyphos,dichlorvos, dicrotophos, dimethylvinphos, fospirate, heptenophos,methocrotophos, mevinphos, monocrotophos, naled, naftalofos,phosphamidon, propaphos, TEPP and tetrachlorvinphos; organothiophosphateinsecticides such as dioxabenzofos, fosmethilan and phenthoate;aliphatic organothiophosphate insecticides such as acethion, amiton,cadusafos, chlorethoxyfos, chlormephos, demephion, demephion-O,demephion-S, demeton, demeton-O, demeton-S, demeton-methyl,demeton-O-methyl, demeton-S-methyl, demeton-S-methylsulphon, disulfoton,ethion, ethoprophos, IPSP, isothioate, malathion, methacrifos,oxydemeton-methyl, oxydeprofos, oxydisulfoton, phorate, sulfotep,terbufos and thiometon; aliphatic amide organothiophosphate insecticidessuch as amidithion, cyanthoate, dimethoate, ethoate-methyl, formothion,mecarbam, omethoate, prothoate, sophamide and vamidothion; oximeorganothiophosphate insecticides such as chlorphoxim, phoxim andphoxim-methyl; heterocyclic organothiophosphate insecticides such asazamethiphos, coumaphos, coumithoate, dioxathion, endothion, menazon,morphothion, phosalone, pyraclofos, pyridaphenthion and quinothion;benzothiopyran organothiophosphate insecticides such as dithicrofos andthicrofos; benzotriazine organothiophosphate insecticides such asazinphos-ethyl and azinphos-methyl; isoindole organothiophosphateinsecticides such as dialifos and phosmet; isoxazole organothiophosphateinsecticides such as isoxathion and zolaprofos; pyrazolopyrimidineorganothiophosphate insecticides such as chlorprazophos and pyrazophos;pyridine organothiophosphate insecticides such as chlorpyrifos andchlorpyrifos-methyl; pyrimidine organothiophosphate insecticides such asbutathiofos, diazinon, etrimfos, lirimfos, pirimiphos-ethyl,pirimiphos-methyl, primidophos, pyrimitate and tebupirimfos; quinoxalineorganothiophosphate insecticides such as quinalphos andquinalphos-methyl; thiadiazole organothiophosphate insecticides such asathidathion, lythidathion, methidathion and prothidathion; triazoleorganothiophosphate insecticides such as isazofos and triazophos; phenylorganothiophosphate insecticides such as azothoate, bromophos,bromophos-ethyl, carbophenothion, chlorthiophos, cyanophos, cythioate,dicapthon, dichlofenthion, etaphos, famphur, fenchlorphos, fenitrothionfensulfothion, fenthion, fenthion-ethyl, heterophos, jodfenphos,mesulfenfos, parathion, parathion-methyl, phenkapton, phosnichlor,profenofos, prothiofos, sulprofos, temephos, trichlormetaphos-3 andtrifenofos; phosphonate insecticides such as butonate and trichlorfon;phosphonothioate insecticides such as mecarphon; phenylethylphosphonothioate insecticides such as fonofos and trichloronat;phenyl phenylphosphonothioate insecticides such as cyanofenphos, EPN andleptophos; phosphoramidate insecticides such as crufomate, fenamiphos,fosthietan, mephosfolan, phosfolan and pirimetaphos;phosphoramidothioate insecticides such as acephate, isocarbophos,isofenphos, methamidophos and propetamphos; phosphorodiamideinsecticides such as dimefox, mazidox, mipafox and schradan; oxadiazineinsecticides such as indoxacarb; phthalimide insecticides such asdialifos, phosmet and tetramethrin; pyrazole insecticides such asacetoprole, ethiprole, fipronil, pyrafluprole, pyriprole, tebufenpyrad,tolfenpyrad and vaniliprole; pyrethroid ester insecticides such asacrinathrin, allethrin, bioallethrin, barthrin, bifenthrin,bioethanomethrin, cyclethrin, cycloprothrin, cyfluthrin,beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin,cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin,zeta-cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, dimethrin,empenthrin, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate,esfenvalerate, flucythrinate, fluvalinate, tau-fluvalinate, furethrin,imiprothrin, metofluthrin, permethrin, biopermethrin, transpermethrin,phenothrin, prallethrin, profluthrin, pyresmethrin, resmethrin,bioresmethrin, cismethrin, tefluthrin, terallethrin, tetramethrin,tralomethrin and transfluthrin; pyrethroid ether insecticides such asetofenprox, flufenprox, halfenprox, protrifenbute and silafluofen;pyrimidinamine insecticides such as flufenerim and pyrimidifen; pyrroleinsecticides such as chlorfenapyr; tetronic acid insecticides such asspiromesifen; thiourea insecticides such as diafenthiuron; ureainsecticides such as flucofuron and sulcofuron; and unclassifiedinsecticides such as closantel, crotamiton, EXD, fenazaflor, fenoxacrim,flubendiamide, hydramethylnon, isoprothiolane, malonoben, metaflumizone,metoxadiazone, nifluridide, pyridaben, pyridalyl, rafoxanide,triarathene and triazamate and any combinations thereof.

Some of the fungicides that can be employed beneficially in combinationwith the compounds of the present invention include:2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol,8-hydroxyquinoline sulfate, Ampelomyces, quisqualis, azaconazole,azoxystrobin, Bacillus subtilis, benalaxyl, benomyl,benthiavalicarb-isopropyl, benzylaminobenzene-sulfonate (BABS) salt,bicarbonates, biphenyl, bismerthiazol, bitertanol, blasticidin-S, borax,Bordeaux mixture, boscalid, bromuconazole, bupirimate, calciumpolysulfide, captafol, captan, carbendazim, carboxin, carpropamid,carvone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans,copper hydroxide, copper octanoate, copper oxychloride, copper sulfate,copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid,cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammoniumethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet,diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion,diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M,dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorphacetate, dodine, dodine free base, edifenphos, epoxiconazole, ethaboxam,ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol,fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil,fenpropidin, fenpropimorph, fentin, fentin acetate, fentin hydroxide,ferbam, ferimzone, fluazinam, fludioxonil, flumorph, fluopicolide,fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide,flutolanil, flutriafol, folpet, formaldehyde, fosetyl,fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine,guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol,imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadinetriacetate, iminoctadine tris(albesilate), ipconazole, iprobenfos,iprodione, iprovalicarb, isoprothiolane, kasugamycin, kasugamycinhydrochloride hydrate, kresoxim-methyl, mancopper, mancozeb, maneb,mepanipyrim, mepronil, mercuric chloride, mercuric oxide, mercurouschloride, metalaxyl, mefenoxam, metalaxyl-M, metam, metam-ammonium,metam-potassium, metam-sodium, metconazole, methasulfocarb, methyliodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone,mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol,octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl,oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate,penconazole, pencycuron, pentachlorophenol, pentachlorophenyl laurate,penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide,picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate,potassium hydroxyquinoline sulfate, probenazole, prochloraz,procymidone, propamocarb, propamocarb hydrochloride, propiconazole,propineb, proquinazid, prothioconazole, pyraclostrobin, pyrazophos,pyributicarb, pyrifenox, pyrimethanil, pyroquilon, quinoclamine,quinoxyfen, quintozene, Reynoutria sachalinensis extract, silthiofam,simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodiumpentachlorophenoxide, spiroxamine, sulfur, SYP-Z071, tar oils,tebuconazole, tecnazene, tetraconazole, thiabendazole, thifluzamide,thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid,triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph,trifloxystrobin, triflumizole, triforine, triticonazole, validamycin,vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusariumoxysporum, Gliocladium spp., Phlebiopsis gigantean, Streptomycesgriseoviridis, Trichoderma spp.,(RS)-N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide,1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate,1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane,2-(2-heptadecyl-2-imidazolin-1-yl)ethanol,2,3-dihydro-5-phenyl-1,4-dithiine 1,1,4,4-tetraoxide,2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride,2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine,4-(2-nitroprop-1-enyl)phenyl thiocyanateme: ampropylfos, anilazine,azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox,bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl,bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmiumcalcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone,chloraniformethan, chlorfenazole, chlorquinox, climbazole, copperbis(3-phenylsalicylate), copper zinc chromate, cufraneb, cuprichydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram,decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol,dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin,drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf,fenapanil, fenitropan, fluotrimazole, furcarbanil, furconazole,furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin,halacrinate, Hercules 3944, hexylthiofos, ICIA0858, isopamphos,isovaledione, mebenil, mecarbinzid, metazoxolon, methfuroxam,methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride,myclozolin, N-3,5-dichlorophenyl-succinimide,N-3-nitrophenylitaconimide, natamycin,N-ethylmercurio-4-toluenesulfonanilide, nickelbis(dimethyldithiocarbamate), OCH, phenylmercurydimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb;prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor,pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole,rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor,thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid,triamiphos, triarimol, triazbutil, trichlamide, urbacid, XRD-563, andzarilamid, and any combinations thereof.

1. A compound of the formula (I)

wherein X represents NO₂, CN or COOR⁴; L represents a single bond; R¹represents methyl or ethyl; R² and R³ independently represent hydrogen,methyl, ethyl, fluoro, chloro or bromo; n is an integer from 0-3; Yrepresents 2-chlorothiazol-4-yl or 3-chloroisoxazol-5-yl; and R⁴represents C₁-C₃ alkyl.
 2. A compound of claim 1 in which X representsNO₂ or CN.
 3. A composition for controlling insects which comprises acompound of any one of claim 1 in combination with aphytologically-acceptable carrier.
 4. A method of controlling insectswhich comprises applying to a locus where control is desired aninsect-inactivating amount of a compound of any one of claims 1-3.